Jin Hui, Su Jingmei, Garmy-Susini Barbara, Kleeman Jeanine, Varner Judy
John and Rebecca Moores Comprehensive Cancer Center, University of California at San Diego, San Diego, California, USA.
Cancer Res. 2006 Feb 15;66(4):2146-52. doi: 10.1158/0008-5472.CAN-05-2704.
Monocytes and macrophages extensively colonize solid tumors, where they are thought to promote tumor angiogenesis. Here, we show that integrin alpha4beta1 (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization. Antagonists of integrin alpha4beta1, but not of other integrins, blocked the adhesion of monocytes to endothelium in vitro and in vivo as well as their extravasation into tumor tissue. These antagonists prevented monocyte stimulation of angiogenesis in vivo, macrophage colonization of tumors, and tumor angiogenesis. These studies indicate the usefulness of antagonists of integrin alpha4beta1 in suppressing macrophage colonization of tumors and subsequent tumor angiogenesis. These studies further indicate that suppression of myeloid cell homing to tumors could be a useful supplementary approach to suppress tumor angiogenesis and growth.
单核细胞和巨噬细胞广泛浸润实体瘤，据认为它们在肿瘤中促进肿瘤血管生成。在此，我们表明整合素α4β1（VLA4）促进髓样细胞对肿瘤的侵袭以及随后的新血管形成。整合素α4β1而非其他整合素的拮抗剂，在体外和体内均阻断单核细胞与内皮细胞的黏附以及它们向肿瘤组织的外渗。这些拮抗剂可预防体内单核细胞对血管生成的刺激、巨噬细胞在肿瘤中的定植以及肿瘤血管生成。这些研究表明整合素α4β1拮抗剂在抑制巨噬细胞在肿瘤中的定植以及随后的肿瘤血管生成方面具有效用。这些研究进一步表明，抑制髓样细胞归巢至肿瘤可能是抑制肿瘤血管生成和生长的一种有用的辅助方法。
